Mathematical modeling of growth and production of alcohol oxidase by Hansenula polymorpha grown on methanol–glucose mixtures

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Abstract
The modeling of growth and production of methanol oxidase (MOX) by Hansenula polymorpha CBS 4732 has been studied to provide a mathematical description of such production processes. Two kinds of mathematical models were constructed for growth on methanol and on mixtures of methanol and glucose. The model for growth on methanol as the sole carbon source consists of kinetics expressions, a limited number of key steps incorporating substrate and production inhibition. This model was used to predict and simulate the culture dynamics at the start‐up, the most critical step in continuous cultivation. The growth on mixtures of methanol and glucose was modeled assuming virtually independent metabolic pathways. The induction and production of MOX could be described by adaptation of various repression equations for various data from the literature. The models describe both experimental data and literature data on growth of H. polymorpha CBS 4732 on glucose–methanol mixtures satisfactorily. All parameters for the induction–repression model for growth of H. polymorpha CBS 4732 on glucose–methanol mixtures yielded evidence that a similar induction–repression pattern is involved in MOX production. Catalase, however, is repressed by a different mechanism.